Merlin, a multi-suppressor from cell membrane to the nucleus.

Abstract

Recent evidence suggests that the neurofibromatosis type 2 (NF2) gene encoded protein merlin suppresses mitogenic signalling not only at the cell membrane but also in the nucleus. At the membrane, merlin inhibits signalling by integrins and tyrosine receptor kinases (RTKs) and the activation of downstream pathways, including the Ras/Raf/MEK/ERK, FAK/Src, PI3K/AKT, Rac/PAK/JNK, mTORC1, and Wnt/β-catenin pathways. In the nucleus, merlin suppresses the E3 ubiquitin ligase CRL4(DCAF1) to inhibit proliferation. Gene expression analysis suggested that CRL4(DCAF1) could also regulate the expression of integrins and RTKs. In this review, we explore the links between merlin function at the membrane and in the nucleus, and discuss the potential of targeting the master regulator CRL4 (DCAF1) to treat NF2 and other merlin-deficient tumours.

• Authors: Lu Zhou, C Oliver Hanemann
• Journal: FEBS letters (FEBS Lett) Vol. 586 Issue 10 Pg. 1403-8 (May 21 2012) ISSN: 1873-3468 [Electronic] England
• PMID: 22595235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• Integrins
• Neurofibromin 2
• Ubiquitin-Protein Ligases
• Receptor Protein-Tyrosine Kinases

Topics

• Animals
• Cell Membrane (metabolism)
• Cell Nucleus (enzymology, metabolism)
• Gene Expression Profiling
• Humans
• Integrins (antagonists & inhibitors, metabolism)
• Mice
• Neurofibromin 2 (metabolism, physiology)
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Signal Transduction (physiology)
• Ubiquitin-Protein Ligases (metabolism)